In 1931 von Euler and Gaddum discovered a smooth muscle stimulating and vasodilating compound in extracts from brain and intestine. The distribution and pharmacology of this compound - called Substance P (SP)-was extensively studied in 1945-60. Since 1970 four important progresses have been made that enable us to make detailed studies on the distribution, pharmacology and physiology of SP. These are a) establishment of the chemical structure of SP b) the synthesis of SP, and the development of c) radioimmunoassay and d) immunofluorescence technique for detection of SP in extracts and tissues. Based on these discoveries the following studies are planned: 1) Further analysis of the specificity and sensitivity of the radioimmunoassay of SP. 2) Detailed studies on the distribution of SP-positive axones and cell bodies of the central and peripheral nervous system using immunofluorescence technique. 3) Occurrence and mode of action of SP in the intestinal wall. Release of SP by mechanical or electrical stimulation of the gut by analyses of local arterial-venous differences of SP. 4) The vasodilating effect of SP on different vascular beds in the dog and on resistance and capacitance blood vessels of the human forearm. 5) The stimulation of SP on exocrine pancreatic and salivary secretion in the dog with simultaneous recording of the local blood flow. 6) Radioimmunological analyses of SP in blood from patients with motility disturbances of the gut, hepatic insufficiency and mental disorders. Post mortem analyses of SP in the brain of patients with psychiatric diseases.